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Wen, Jing; Lv, Ruitu; Ma, Honghui; Shen, Hongjie; He, Chenxi; Wang, Jiahua; Jiao, Fangfang; Liu, Hang; Yang, Pengyuan; Tan, Li; Lan, Fei; Shi, Yujiang Geno; He, Chuan; Shi, Yang; Diao, Jianbo
Molecular cell, 03/2018, Volume: 69, Issue: 6Journal Article
N -methyladenosine (m A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m A methylation. Finally, Zc3h13 depletion, as does WTAP, Virilizer, or Hakai, impairs self-renewal and triggers mESC differentiation. Taken together, our findings demonstrate that Zc3h13 plays a critical role in anchoring WTAP, Virilizer, and Hakai in the nucleus to facilitate m A methylation and to regulate mESC self-renewal.
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